This proposed project is a competing renewal to the Casa Pia Study of the Health Effects of Dental Amalgams in Children, a cooperative agreement funded by the National Institute of Dental and Craniofacial Research as one component of the Children's Amalgam Trial. The University of Washington is the applicant organization with a subcontract to the University of Lisbon, Portugal, as the clinical site. The Study is a randomized clinical trial in which 507 children of ages 8 to 10 at entry with substantial dental treatment needs and who are students of Casa Pia Schools in Lisbon, have been randomized to the use or non-use of mercury amalgams in their dental treatment. The project is currently in the second year of follow-up, with 95% retention thus far in the study. Mercury exposure is measured from urine samples at baseline and follow-up exams at one-year intervals. Four primary endpoints are monitored from baseline at one-year intervals: three neurobehavioral (combined assessments from neurobehavioral tests for attention, memory, and motor/visual motor domains) and one neurological (nerve conduction velocities). Secondary endpoints include two renal (two Glutathione Transferase isozymes specific to renal tubular damage), a clinical neurological exam, porphyrin profiles, urinary albumin levels and the occurrence of sentinel health events. Comparison between the two groups of children for the four primary endpoints are made annually using a combination of Hotelling's T2 test and an extension of the O'Brien test for multiple endpoints adapted for longitudinal data and multiple tests over time. If significant adverse health effects of exposure to dental amalgams (or to the alternative dental material, composites) are detected during the course of the study, the children treated with the harmful material will be re-treated with the other. The purpose of this renewal application is to extend the funding period to cover the seven years of follow-up proposed in the original grant. We intend to continue collecting data in the study po2ulation for the same four endpoints currently in use, with the same methodology as during the initial 3 follow-up years, utilizing the same personnel currently employed. in obtaining the data, with only some minor revisions in the neurobehavioral tests to account for the maturation of the test, population. The introduction of some new secondary endpoints is proposed. This international collaboration has resulted in a study team that has demonstrated its expertise in all relevant areas and its capability to successfully complete this important study and settle the controversy over whether amalgam has even any subtle health effects associated with its use in the most susceptible population, children.